Heterocyclic Thiosemicarbazones Research Articles

Structural Studies of 2,6-Diacetyl- and 2,6-Diformylpyridine Bis(thiosemicarbazones)

Although a large number of crystal structures of heterocyclic thiosemicarbazones have recently appeared in the literature, few structures of heterocyclic bis(thiosemicarbazones) or their metal complexes have been reported. Complexes of iron(II), indium(III), tin(IV), bismuth(III) involve bis(thiosemicarbazones) coordinating as N3S2 pentadentate ligands, often resulting in 7-coordinate complexes. In contrast, complexes with zinc(II) are often binuclear with thiosemicarbazone moieties of a bis(thiosemicarbazone) coordinating to two different zinc centers. Also included in this study is the structure of the first complex with a 2,6-diformylpyridine bis(thiosemicarbazone) ligand, a 4-coordinate nickel(II) complex with unusual coordination.

The Hypolipidemic Activity of Heterocyclic Thiosemicarbazones,Thioureas and Their Metal Complexes in Sprague Dawley Male Rats

Heterocyclic thiosemicarbazones, thioureas and their copper, nickel, and cobalt complexes were shown to be potent hypolipidemic agents in male Sprague Dawley rats at 8 mg/kg/day, orally. These agents lowered the activity of rat hepatic rate limiting enzymes for the synthesis of cholesterol and triglycerides. The effects of these agnets on cytoplasmic ATP-dependent citrate lyase, acetyl CoA synthetase and HMG-CoA reductase activities were reduced by a magnitude to explain the reduction of serum cholesterol levels afforded by the compounds. The reduction of acetyl CoA carboxylase, sn-glycerol-3-phosphate synthetase and phosphotidylate phosphohydrolase activities caused by the derivatives is of sufficient magnitude to explain the observed reduction in serum triglycerides after administration of the agents.

Equilibrium and kinetic studies of iron(II) and iron(III) complexes of some α(N)-heterocyclic thiosemicarbazones. Reduction of the iron(III) complexes of 2-formylpyridine thiosemicarbazone and 2-acetylpyridine thiosemicarbazone by cellular thiol-like reducing agents

α(N)-heterocyclic thiosemicarbazones have been shown to possess antitumor properties in mammalian cells through the inhibition of DNA synthesis; the ability to provide the inhibitory action is probably due to coordination of iron. This paper deals with equilibrium and kinetic studies involving 2-formylpyridine thiosemicarbazone (HFPT) and 2-acetylpyridine thiosemicarbazone (HAPT) coordinated to Fe(II) and Fe(III) cations in aqueous solution. The formation constants of all species present in equilibrium were determined. Kinetic measurements of the reduction of the Fe(III) complex of both ligands by thiolic reducing agents, that can act as structural models of cellular thiols, i.e., N-acetyl-L-cysteine (ACCIS) and dithiothreitol (DTT), were carried out. The experimental data lead to a rate law of the type v = k 1[A] + k 2[A][B], where [A] represents the concentration of the complex and [B] that of the reducing agent, indicating the coexistence of two reaction pathways. One pathway depends only on the complex concentration and occurs even in the absence of the reducing agent, and the other involves both the complex and ACCIS or DTT.

Symmetrisation, isomerism and structural studies on novel phenylmercury(II) thiosemicarbazonates: correlation of the energy barrier to rotation of the amino group with the bonding parameters of the thioamide group

The reactions of phenylmercury(II) acetate with a series of alkyl, aryl and heterocyclic thiosemicarbazones in ethanol formed novel phenylmercury(II) derivatives of stoichiometry [HgPhL] [HL = RN3N2HC1(S)N1H2 = cyclopentanone 1, cyclohexanone 2, benzaldehyde 3, 2-hydroxybenzaldehyde 4, 4-methoxybenzaldehyde 5, pyrrole-2-carbaldehyde 6, thiophene-2-carbaldehyde 7 or furan-2-carbaldehyde 8 thiosemicarbazone], characterised with the help of analytical data, physical properties, IR, far-IR, multinuclear NMR (1H, 13C, 199Hg) spectroscopy and X-ray crystallography of complexes 1, 5 and 6. The 1H and 13C NMR data suggest that the N2H group is deprotonated during reaction with phenylmercury(II) acetate and co-ordination occurs via the N3,S atoms in a chelating mode. The 199Hg NMR data suggest symmetrisation phenomenon for complexes 3 and 5, 2[HgPhL] ⇌ HgPh2 + [HgL], which is supported also by 1H and 13C NMR data. The δ(Hg) values reveal that shielding of Hg with the change of organic group in the thiosemicarbazones decreases in the order: 2-hydroxybenzene ⋙ furan > benzene > 4-methoxybenzene thiophene ≈ cyclohexanone ≈ cyclopentanone > pyrrole and the Lewis basicity of the thiosemicarbazones varies in the opposite order. The 1H and 13C NMR data reveal that 7 and 8 show isomerism. There are two strong [Hg–C 2.063(7) 1, 2.069(10) 5, 2.049(11) 6; Hg–S 2.382(2) 1, 2.357(3) 5, 2.377(3) A 6] and one weak bond [Hg–N3 2.489(6) 1, 2.611(7) 5, 2.492(9) A 6], with CPh–Hg–S bond angles of 162.9(2), 174.2(3), 165.8(3)° respectively. The weak intermolecular interactions via Hg · · · N2 [3.001(6) A] in 1 and via Hg · · · S in 5 [3.518(3) A] and 6 [3.528(3) A] form centrosymmetric dimers and Hg formally acquires four-co-ordination with two strong (Hg–C, Hg–S), one weak (Hg · · · N3) and one secondary (Hg · · · N2 or S) bonds. The preferred dimer formation via N2 nitrogen in 1, rather than via sulfur atoms (5 and 6) despite Hg · · · S affinity represents an unusual bonding mode. From the low-temperature 1H NMR studies of some selected complexes, the energy barrier (ΔGTc*, Tc is coalescence temperature) to rotation of the amino group about the C1–N1 bond was calculated and correlated with bonding parameters of the thioamide group in the solid state.

Synthesis, Characterization and Molecular Structures of someBismuth(III) Complexes with Thiosemicarbazones andDithiocarbazonic Acid Methylester Derivatives with Activityagainst Helicobacter Pylori

The reactions of bismuth(III) nitrate pentahydrate and bismuth(III) chloride with heterocyclic thiosemicarbazones and derivatives of dithiocarbazonic acid methylester were used to synthesize the respective bismuth(III) complexes, which could be divided into five groups D-H because of their stoichiometrical properties and their molecular structures. The molecular structure and the near coordination sphere of the bismuth(III) central atom of four representative compounds were determined by single-crystal X-ray studies. Bis[1-azepanyl-4-(2-pyridyl)-2,3-diazapenta-1,3-diene-1-thiolato-N′,N3,S]bismuth(III) nitrate (5) belongs to group D. The two tridentate ligands and the nitrate ion surround the bismuth atom. The best description of the coordination sphere appears to be that of a distorted trigonal dodecahedron with one position occupied by the lone pair of the bismuth atom. Bis[1-azepanyl-4-(2-thienyl)-2,3-diazapenta-1,3-diene-1-thiolato-N3,S]bismuth(III) nitrate (9) is assigned to complex type E. Here, two deprotonated ligand molecules are coordinated to the bismuth(III) central atom as bidentate ligands. The structure of this complex can best be described as a distorted trigonal antiprism with a five-coordinated central atom. The two triangular faces are formed by the atoms S(4), N(6), O(11) and S(3), N(4) and the lone pair of the central atom. The two chelate rings are almost perpendicular to each other. Complex molecules of group F form dimeric units with bichloro-bridged bismuth atoms. The structure of di-μ-chlorobis[1-azepanyl-4-(2-pyridyl)-2,3-diazapenta-1,3-diene-1-thiolato-N′,N3,S-chloro]dibismuth(III) (15) can be described as two six-coordinated bismuth atoms, which are bound together via two bridging chlorine atoms. The two bismuth atoms Bi(1) and Bi(1a) and the two bridging chlorine atoms Cl(2) and Cl(2a) form the Bi2Cl2 plane. The two tridentate ligand molecules coordinate via the same atoms as shown in complex 5. In addition, they form two parallel planes, which are perpendicular to the Bi2Cl2 plane. With regard to the center of the Bi(1)-Bi(2) axis they are central point symmetrical, i.e. one pyridine ring lies above and the other beneath the Bi2Cl2 plane. Bismuth(III) chloride and pyridine-2-carboxaldehydethiosemicarbazone 1 b or 2-acetylpyridine-thiosemicarbazone 1 c form complexes of group G. Three chlorine atoms and a bidentate ligand are coordinated to the bismuth(III) central atom. The bidentate ligand bound to the central atom through the N(3) atom and the sulfur atom of the thioketo group. The structure of 18 is completely different from the structures of the bismuth(III) complexes discussed so far and was therefore assigned to group H. The bismuth central atom is coordinated with two ligands, which are bound in different ways. One of them is deprotonated. This ligand is bound to the central atom via the sulfur atom S(3) of the thiolate group and the N(5) atom. An interaction between the sulfur atom of the thiophene ring and the bismuth atom is not possible.The other ligand molecule is not deprotonated. This ligand is bound to the bismuth(III) cation merely via the sulfur atom S(1) of the thioketo group. The best description of the coordination sphere of the bismuth atom is that of a distorted square bipyramidal polyhedron. The square face is formed by the atoms S(3), N(5), Cl(1), the lone pair and the bismuth atom within. The axial positions are occupied by the atoms S(1) and Cl(2). The bond angle between S(1), Bi(1) and Cl(2) differs by about eight degrees from the value determined for a regular square bipyramidal polyhedron of 180 degrees. Some of the newly synthesized bismuth complexes and three ligands have been tested against several strains of Helicobacter pylori bacteria in an agar dilution test. Almost all of the listed bismuth complexes show excellent inhibitory properties with regard to growth of H. pylori already at low concentrations.

STUDIES ON BINUCLEAR COMPLEXES DERIVED FROM SULFUR CONTAINING ORGANIC MOIETIES

Abstract Synthetic, spectroscopic and biological features of some binuclear complexes with monofunctional bidentate heterocyclic thiosemicarbazones have been described. The resulting derivatives of the type, B(TSCZ) (where TSCZ 1 represents the anion of thiosemicarbazone moiety) are colored solids and non-electrolytic in nature. On the basis of analytical data, IR, 1H, 13C and 11B NMR spectral studies, a tri-coordinated environment for boron and a penta-coordinated environment around arsenic may be assigned to the resulting binuclear complexes. Some representative ligands as well as their binuclear complexes have also been evaluated for their antifungal and antibacterial activities.

SYNTHESIS, CHARACTERIZATION AND BIOCIDAL EFFECTS OF TRIORGANOLEAD(IV) COMPLEXES DERIVED FROM THIO-LIGANDS

Abstract The substitution reactions of heterocyclic thiosemicarbazones with triphenyllead(IV) chloride in 1:1 molar ratio give Ph3PbL (L = anion of thiosemicarbazone derived from heterocyclic aldehyde or ketone) type of complexes. The elemental analyses, molecular weight determinations, conductivity measurements and spectral (IR, 1H and 13C NMR) studies have been used to elucidate their penta-coordinated structures. Some representative ligands and their metal chelates have also been screened for their antimicrobial effects against different species of pathogenic fungi and bacteria.

The cytotoxicity of heterocyclic thiosemicarbazones and their metal complexes on human and murine tissue culture cells

Heterocyclic thiosemicarbazones, thioureas and 2-substituted pyridine N-oxides as well as representative nickel, cobalt and copper complexes were shown to be potent antineoplastic/cytotoxic agents. The cytotoxicity was demonstrated against single cell leukemia as well as cell lines derived from solid tissue (colon adenocarcinoma, HeLa, KB, skin, bronchogenic lung, bone osteosarcoma and glioma). In L1210 cells, DNA synthesis and subsequently RNA synthesis were particularly inhibited by the agents. IMP dehydrogenase activity and thus purine de novo synthesis was reduced significantly by the agents. Dihydrofolate reductase, ribonucleoside reductase, nucleoside kinase and DNA polymerase alpha activities were inhibited by the agents. d(NTP) pool levels were reduced by most of the agents. DNA strand scission was present with all of the derivatives; however, there was no evidence of intercalation, cross linking or alkylation/binding to bases of DNA. This new group of compounds may offer novel exploratory derivatives for future investigations in the treatment of cancer.

The cytotoxicity of copper(II) complexes of heterocyclic thiosemicarbazones and 2-substituted pyridine N-oxides

Thiosemicarbazone complexes of copper(II) were shown to be potent cytotoxic/antineoplastic agents against the growth of murine and human tumor cells. Selectivity of some agents was demonstrated against specific solid tumor growth. In L1210 lymphoid leukemia cells the copper complexes preferentially inhibited DNA synthesis with their major effects on the purine de novo pathway at PRPP amido transferase, IMP dehydrogenase and dihydrofolate reductase. The reductions of purines correlated positively with inhibition of DNA synthesis and cytotoxicity of the agents tested. DNA itself was fragmented after incubation with the drug; however, no binding of the agent to nucleotide bases or intercalation between base pairs was evident.

ChemInform Abstract: Antifungal, Antibacterial, and Antifertility Activities of Biologically Active Heterocyclic Thiosemicarbazones and Their Coordination Complexes with the Dimethylsilicon Moiety.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

SPECTRAL CHARACTERIZATION AND ANTIFUNGAL ACTIVITY OF SOME NEWLY SYNTHESIZED SULFUR CONTAINING TRIORGANOTIN(IV) DERIVATIVES

Abstract Triorganotin(IV) complexes having an azomethine linkage have been prepared by the substitution reactions of trimethyl tin chloride with heterocyclic thiosemicarbazones and characterized by elemental analyses, molecular weight determinations and conductivity measurements. On the basis of infrared, 1H, 13C and 119Sn NMR spectroscopy studies, a trigonal bipyramidal geometry for the resulting complexes has been proposed. The nitrogen atom occupies the axial site, while two methyl groups rest in equatorial positions. The antifungal activity of some of the ligands and their metal complexes has also been evaluated against different pathogenic fungi.

Antifungal and antitumor activity of heterocyclic thiosemicarbazones and their metal complexes: current status.

More than 75 substituted thiosemicarbazones and a number of metal complexes of each have been assayed for their antifungal activity. Their activity is significantly affected by the substituted groups attached at both 1N and 4N of the thiosemicarbazone moiety. Greatest activity occurs for 2-substituted pyridine thiosemicarbazones with differences observed for 2-formylpyridine, 2-acetylpyridine and 2-benzoylpyridine derivatives and their metal complexes. Further, there are activity differences for 4N-alkyl-, 4N-aryl-, 4N-dialkyl- and 3-azacyclothiosemicarbazones and their metal complexes as well as changes in the substituent size among each of these subgroups. Cu(II) complexes are often more active than the uncomplexed thiosemicarbazones, with the latter showing similar activity to Ni(II) complexes in many instances. The reduction potential of the thiosemicarbazone ligand in a Cu(II) complex, the strength of the ligand field and various spectral properties can be correlated to the inhibitory activity.

Synthesis and Characterization of Potential Antitumor and Antiviral Gallium(III) Complexes of α-(N)-Heterocyclic Thiosemicarbazones

Abstract Gallium(III) complexes of six α-(N)-heterocyclic thiosemicarbazones were synthesized and characterized by elemental analysis, conductivity measurements, infrared spectroscopy and 1H NMR spectroscopy. Mass spectrometry was carried out with two complexes and a X-ray single-crystal study performed with one complex - dichloro-[(2-acetylpyridine)-4, 4-(3-methyl pentamethylene) thiosemicarbazonato-N1, N2, S]gallium(III). The gallium(III) complexes had the general formula LGaCL2 (LH [ligand acid] = 2-formylpyridine thiosemicarbazone, 2-acetylpyridine thiosemicarbazone, 2-aceryl-pyridine-4, 4-dimethyl thiosemicarbazone, 2-acetylpyridine-4, 4-hexamethylene thiosemicarbazone, 2-acetylpyridine-4, 4-(cyclohexane-l, 4-bismethylene) thiosemicarbazone, 2-acetylpyridine-4, 4-(3-methyl pentamethylene) thiosemicarbazone). The galhum(III) complexes of 2-formylpyridine and 2-acetylpyridine thiosemicarbazone seem to have a cis-configurated trigonal bipyramidal structure whereas the galhum(III) complexes of the N4-dis...

A FACILE SYNTHESIS OF THIOSEMICARBAZIDESAND THIOSEMICARBAZONES BY THETRANSAMINATION OF 4-METHYL-4-PHENYL-3-THIOSEMICARBAZIDE

Abstract Thiosemicarbazones of α-(N)-heterocyclic ketones and aldehydes possess a broad spectrum of potentially useful chemotherapeutic activities. Thus, the antimalarial, antibacterial, and antiviral properties of this class have been explored by Klayman, et al.1 The antileishmanial activity of a series of acetyl β-carboline thiosemicarbazones was recently described by Dodd and coworkers .2 The α-(N)-heterocyclic thiosemicarbazones act as tridentate ligands for transition metals3; this property has been implicated in their biological mechanism of action.4 The synthesis thiosemicarbazone-transition metal complexes and the spectroscopic investigation of structure and bonding in these complexes is being actively pursued 5 In order to facilitate these investigations, an improved method of synthesizing thiosemicarbones is desirable. Such a synthesis should be efficient (high yield), general (afford thiosemicarbazones of N4-monosubstitution or N4,N4-disubstitution patterns), safe (avoids toxic or unpleasant re...

Antifungicidal, antibacterial and antifertility activities of biologically active heterocyclic thiosemicarbazones and their coordination complexes with the dimethylsilicon moiety

AbstractSynthetic, structural and biological aspects of trigonal‐bipyramidal, Me2Si(NS)Cl and octahedral, Me2Si(NS)2 types of organosilicon (IV) complexes of heterocyclic thiosemicarbazones (NSH) have been described. The complexes were characterized by elemental analysis, molecular weight determination, conductance measurements and electronic, infrared, 1H and 13C NMR spectral studies. Some ligands and their corresponding dimethylsilicon (IV) complexes have been tested for their effects on several pathogenic fungi and bacteria. Two representative complexes have also been found to act as sterilizing agents by reducing the production of sperm in male mice.

Copper complexes of pyridine 2-aldehyde and 2-acetylpyridine thiosemicarbazones

Copper complexes of two heterocyclic thiosemicarbazones were synthesized and characterized by magnetic-moment measurement, and ESR and IR spectroscopy. Implications of the magnetic and spectral data in relation to the structures of the complexes are discussed.

Heterocyclic semicarbazones and thiosemicarbazones. XLIX. Antiinflammatory activity of isatin thiosemicarbazones and their cyclization products

Heterocyclic semicarbazones and thiosemicarbazones. XLIX. Antiinflammatory activity of isatin thiosemicarbazones and their cyclization products

Heterocyclic semicarbazones and thiosemicarbazones. XLVI. Activity of acylhydrazones of α-dicarbonyl compounds toward influenza virus

Heterocyclic semicarbazones and thiosemicarbazones. XLVI. Activity of acylhydrazones of α-dicarbonyl compounds toward influenza virus

ChemInform Abstract: HETEROCYCLIC SEMICARBAZONES AND THIOSEMICARBAZONES. 43. SPECTRA AND STRUCTURE E OF ISATIN‐2‐THIOCARBONYLHYDRAZONES

Chemischer InformationsdienstVolume 10, Issue 32 Physical Organic Chemistry ChemInform Abstract: HETEROCYCLIC SEMICARBAZONES AND THIOSEMICARBAZONES. 43. SPECTRA AND STRUCTURE E OF ISATIN-2-THIOCARBONYLHYDRAZONES A. B. TOMCHIN, A. B. TOMCHINSearch for more papers by this authorK. N. ZELENIN, K. N. ZELENINSearch for more papers by this authorG. A. SHIROKII, G. A. SHIROKIISearch for more papers by this author A. B. TOMCHIN, A. B. TOMCHINSearch for more papers by this authorK. N. ZELENIN, K. N. ZELENINSearch for more papers by this authorG. A. SHIROKII, G. A. SHIROKIISearch for more papers by this author First published: August 7, 1979 https://doi.org/10.1002/chin.197932102AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume10, Issue32August 7, 1979 RelatedInformation

Inhibition of the particle-associated RNA-dependent RNA polymerase activity of influenza viruses by chelating agents.

SUMMARY Approximately 0.05 mm concentrations of the chelating agents bathocuproine and bathophenanthroline disulphonic acid disodium salts, which form very stable complexes with ‘soft’ heavy-metal ions such as zinc, inhibited in vitro the RNA-dependent RNA polymerase activity associated with influenza B/LEE/40 and A/RI-5+ (H2N2) viruses in the presence of a large molar excess of Mn(II) and Mg(II). Certain heterocyclic thiosemicarbazones also inhibited influenza RNA polymerase activity, although complete inhibition was not detected even with high concentrations (0.1 mm) of the compounds. Analogues of the active heterocyclic thiosemicarbazones, such as isatin 3-semicarbazone, which have reduced chelating activities for zinc, also had reduced inhibitory effects on influenza virus associated RNA polymerase activity. However, inhibition of influenza RNA polymerase activity by 0.1 mm-bathocuproine or 0.1 mm-isatin 3-thiosemicarbazone was not reversed by the addition of molar equivalent or excess concentrations of zinc. Relatively high concentrations of the chelating agents had no detectable effect on the haemagglutinin, neuraminidase or infectivity titres of influenza B/LEE/40 virus. The chelating agents may inhibit influenza virus-associated RNA polymerase activity by the formation of a ternary complex of enzyme-metal-ligand.